PROJECT SUMMARY The prevalence of apraxia of speech (AOS) among individuals with a non-fluent variant of primary progressive aphasia (PPA) is estimated to be 80%,10 and is often considered the most salient and debilitating aspect of disease progression for this subset of patients. In addition, AOS is a core diagnostic inclusion criterion for the non-fluent variant of PPA,14 making the detection and characterization of apraxic speech crucial in a clinical setting. However, it remains difficult to characterize apraxic speech deficits in this population, due in large part to a lack of understanding of the mechanisms of speech motor control that underlie these deficits. The lack of mechanistic understanding also handicaps the development of behavioral intervention approaches since little is known about underlying disordered speech control processes that could serve as effective targets of treatment. Therefore, there is a need for research that investigates the mechanisms of speech motor control that underlie AOS in PPA. Prior research in other neurologically impaired populations suggests that AOS is caused by impaired feedforward speech motor control processes. In the proposed research, we will use behavior- and imaging-based analyses to investigate the integrity of feedforward speech motor control processes in individuals with concomitant PPA and AOS. In Aim 1, we will use an auditory masking paradigm to assess the effect of feedback inhibition (i.e., forced reliance on feedforward control networks) on speech motor performance for a group of individuals with both PPA and AOS (PPA/+AOS), as compared to a group of individuals with PPA only (PPA/-AOS), and a group of healthy age-matched controls (HC). Prior research on feedback inhibition in a stroke-induced aphasic population, as well as preliminary data out of our lab, suggest that feedback inhibition will lead to a proportionally greater decrement in speech production performance for the PPA/+AOS group as compared to either the PPA/-AOS or HC groups. In Aim 2, we will correlate the change in speech production performance due to feedback inhibition with MRI-derived measures of cortical thickness in three hypothesis-driven regions of interest (ROIs). Our preliminary data has indicated cortical atrophy associated with slowed articulator movement in select regions related to motor speech function, including the ventral premotor and supplementary motor cortices. The overall goal of the proposed research is to evaluate the integrity of feedforward speech control networks among individuals with concomitant PPA and AOS, and in this way, advance the understanding of AOS as it occurs in PPA. Results of this research will provide further experimental validation of computational speech production models and most importantly, will be used to inform approaches to characterization and intervention in the clinical setting.